1. Field of the Invention
The present invention relates to quinazolinone derivatives, their acid-addition salt or their quaternary ammonium salt, having an effect of preventing overload of calcium ions (Ca.sup.2+) in cells, as well as their usages.
2. Description of the Prior Art
Overload of calcium ions (Ca.sup.2+) in cells has been regarded as an important matter in the cell injury mechanism after ischemia or reperfusion. See, for example, Annu. Rev. Physiol., 1990, 52, 543-559. Cell injuries caused by ischemia or reperfusion are observed in many diseases routinely encountered, and those in heart, brain and kidney, among others, are serious problems experienced clinically. Thus, an agent preventing overload of calcium ions could be a useful preventing or treating agent for ischemic heart disease, ischemic cerebral disease and ischemic renal disease.
Heretofore, a calcium antagonist has been used as an agent for preventing the influx of calcium ions into myocardial cells or blood vessel smooth muscle cells. However, its effect on the overload of calcium ions in myocardial cells after ischemia or reperfusion is not satisfactory. Thus, an agent for preventing the calcium overload has been keenly desired.
Calcium ion overload induces injuries in myocardial cells or smooth muscle cells, such as disorders, not only in case of ischemia, but in the contraction and relaxation function and in the energy metabolism, as well as morphological damages and electro-physiological disorder, thus causing diseases in the circulatory organs. See, for example, Cardionvasc. Res., 1986, 20, 645-651. Accordingly, an agent for preventing calcium ion overload could be a useful preventing or treating agent for circulatory diseases, such as heart failure, hypertension and arrhythmia.